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K A Hossmann

Publications and source records attributed to K A Hossmann.

At least 91 records · Page 5Linked to original sources
PubMed1996

Early ultrastructural changes after brief histotoxic hypoxia in cultured cortical and hippocampal CA1 neurons.

Primary cortical and hippocampal neuronal cultures submitted to brief histotoxic hypoxia suffer delayed neuronal death after 24 h [Uto et al. (1995) J Neurochem 64: 2185-2192]. In this study the ultrastructural changes were monitored during the first 6 h following 5-min histotoxic hypoxia induced by exposure to 100 microM iodoacetate. In both cortical and hippocampal CA1 neurons, disaggregation of ribosomes was the earliest sign of histotoxic pathology. Vacuolizations of mitochondria, endoplasmic reticulum and Golgi apparatus, as well as fragmentation and disintegration of neurofilaments followed later. Signs of apoptotic nuclear degeneration were absent. Our observations demonstrate that, similar to that seen in ischemia, disaggregation of ribosomes after brief histotoxic hypoxia is one of the first pathological alterations heralding delayed neuronal death.

Animals↗
PubMed1996

Volume expansion during cardiopulmonary resuscitation reduces cerebral no-reflow.

Resuscitation of the brain after cardiac arrest requires homogeneous blood recirculation which, however, may be impaired by low reperfusion pressure, intravascular coagulation, increased blood viscosity and endothelial cell swelling. Intravascular volume expansion induced by intravenous infusion of a small volume of hypertonic solution has previously been shown to improve nutritional flow to the brain after severe hemorrhage shock. We therefore investigated whether this therapy also improves cerebral reperfusion after cardiopulmonary resuscitation. Fourteen adult normothermic cats were resuscitated after 15 min of ventricular fibrillation by closed-chest cardiac massage in combination with epinephrine, bicarbonate and DC-defibrillations. Eight animals were submitted to the standard resuscitation protocol. Six cats received additionally 2 ml/kg/10 min 7.5% NaCl/6% hydroxyethyl starch solution for post-ischemic volume expansion. EEG, ECG, CBF, and the aortic, left ventricular, central venous and intracranial pressures were monitored. Reperfusion of the brain was visualized 30 min after cardiac resuscitation by labelling the circulating blood with fluorescein isothiocyanate albumin. Areas of impaired brain reperfusion (no-reflow)-defined by the absence of microvascular filling-were identified by fluorescence microscopy at eight standard coronal levels of the forebrain, and expressed as percent of total sectional area. All animals were successfully resuscitated although volume expansion decreased myocardial and cerebral reperfusion pressure during cardiopulmonary resuscitation. Treatment with hypertonic solution increased serum osmolality transiently and prevented hemoconcentration throughout the experiment. Cerebral no-reflow was significantly reduced from 28 +/- 13% to 15 +/- 6% of total forebrain sectional area. Volume expansion by small volume hypertonic solutions may, therefore, improve recovery of brain function following cardiac arrest.

Animals↗
PubMed1996

Susceptibility of hippocampal and cortical neurons to argon-mediated in vitro ischemia.

Neurons from cerebral cortex and hippocampal CA1 sector exhibit a striking difference in vulnerability to transient ischemia. To establish whether this difference is due to the inherent (pathoclitic) properties of these neurons, the ischemic susceptibility was studied in primary cortical and hippocampal cultures by using a new model of argon-induced in vitro ischemia. Neuronal cultures were exposed at 37 degrees C for 10-30 min to argon-equilibrated glucose-free medium. During argon equilibration, Po2 declined to < 2.5 torr within 1 min and stabilized shortly later at approximately 1.3 torr. After 30 min of in vitro ischemia, total adenylate was < 45% and ATP content < 15% of control in both types of culture. Cytosolic calcium activity increased from 15 to 50 nM. Reoxygenation of cultures after in vitro ischemia led to delayed neuronal death, the severity of which depended on the duration of in vitro ischemia but not on the type of neuronal cultures. Energy charge of adenylate transiently returned to approximately 90% of control after 3 h, but ATP content recovered only to 40% and protein synthesis to < 35%. Cytosolic calcium activity continued to rise after ischemia and reached values of approximately 500 nM after 3 h. The new argon-induced in vitro ischemia model offers major advantages over previous methods, but despite this improvement it was not possible to replicate the differences in cortical and hippocampal vulnerability observed in vivo. Our study does not support the hypothesis that selective vulnerability is due to an inherent pathoclitic hypersensitivity.

Adenine Nucleotides↗
PubMed1996

Potassium-induced cortical spreading depressions during focal cerebral ischemia in rats: contribution to lesion growth assessed by diffusion-weighted NMR and biochemical imaging.

In focal ischemia of rats, the volume of ischemic lesion correlates with the number of peri-infarct depolarizations. To test the hypothesis that depolarizations accelerate infarct growth, we combined focal ischemia with externally evoked spreading depression (SD) waves. Ischemic brain infarcts were produced in halothane-anaesthetized rats by intraluminal thread occlusion of the middle cerebral artery (MCA). In one group of animals, repeated SDs were evoked at 15-min intervals by microinjections of potassium acetate into the frontal cortex. In another group, the spread of the potassium-evoked depolarizations was prevented by application of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801). The volume of ischemic lesion was monitored for 2 h by diffusion-weighted imaging (DWI) and correlated with electro-physiological recordings and biochemical imaging techniques. In untreated rats, each microinjection produced an SD wave and a stepwise rise of the volume and signal intensity of the DWI-visible cortical lesion. The volume of this lesion increased between 15 min and 2 h of MCA occlusion from 19 +/- 15% to 66 +/- 16% of ipsilateral cortex. In dizocilpine-treated animals, microinjections of potassium did not evoke SDs, nor did the volume and signal intensity of the DWI-visible cortical lesion change. At 15 min after MCA occlusion, the DWI-visible lesion was larger than in untreated animals-43 +/- 16% of the ipsilateral cortex; however, after 2 h, it increased only slightly further to 49 +/- 21%. Slower lesion growth in the absence of SDs was also reflected by the volume of ATP-depleted tissue, which, after 2 h of MCA occlusion, involved 26 +/- 12% of the ipsilateral cortex in treated and 49 +/- 9% in untreated animals (p < 0.01). These observations support the hypothesis that peri-infarct depolarizations accelerate cerebral infarct growth.

Animals↗
PubMed1996

Brief hypercapnia enhances somatosensory activation of blood flow in rat.

Activation of CBF by hypercapnia or functional stimulation has been attributed to multiple mediators, most of which are thought to interfere with cerebrovascular reactivity in a closely time-related manner. Here we describe that brief hypercapnia produces marked up-regulation of somatosensory activation of blood flow that outlasts carbon dioxide exposure for at least 60 min. In chloralose-anesthetized, mechanically ventilated rats, somatosensory activation was carried out by electrical stimulation of the forepaw. Blood flow was measured in the contralateral primary somatosensory cortex by laser-Doppler flowmetry (LDF). Under control conditions, somatosensory stimulation increased LDF by 38.8 +/- 11.0%. Ventilation with 6% CO2 for 3 min caused a rise of LDF by 28.0 +/- 8.7%. Baseline CBF and PaCo2 returned to control values within 20 min. Repetition of somatosensory stimulation after hypercapnia revealed a long-lasting up-regulation of the flow response: 25 min after hypercapnia, functional stimulation increased LDF by 86.0 +/- 18.1%, and 60 min after hypercapnia even by 96.0 +/- 26.0%. This is the first demonstration of CO2-induced up-regulation of functional activation of blood flow and an example of the importance of general physiological variables for the modulation of the coupling process.

Animals↗
PubMed1996

Cerebral resuscitation from cardiac arrest: pathophysiologic mechanisms.

Both the period of total circulatory arrest to the brain and postischemic-anoxic encephalopathy (cerebral postresuscitation syndrome or disease), after normothermic cardiac arrests of between 5 and 20 mins (no-flow), contribute to complex physiologic and chemical derangements. The best documented derangements include the delayed protracted inhomogeneous cerebral hypoperfusion (despite controlled normotension), excitotoxicity as an explanation for selectively vulnerable brain regions and neurons, and free radical-triggered chemical cascades to lipid peroxidation of membranes. Protracted hypoxemia without cardiac arrest (e.g., very high altitude) can cause angiogenesis; the trigger of it, which lyses basement membranes, might be a factor in post-cardiac arrest encephalopathy. Questions to be explored include: What are the changes and effects on outcome of neurotransmitters (other than glutamate), of catecholamines, of vascular changes (microinfarcts seen after asphyxia), osmotic gradients, free-radical reactions, DNA cleavage, and transient extracerebral organ malfunction? For future mechanism-oriented studies of the brain after cardiac arrest and innovative cardiopulmonary-cerebral resuscitation, increasingly reproducible outcome models of temporary global brain ischemia in rats and dogs are now available. Disagreements exist between experienced investigative groups on the most informative method for quantitative evaluation of morphologic brain damage. There is agreement on the desirability of using not only functional deficit and chemical changes, but also morphologic damage as end points.

Altitude Sickness↗
PubMed1996

Periinfarct depolarizations.

In the surroundings of focal ischemic lesions, repetitive spreading depression (SD)-like depolarizations occur. These depolarizations are triggered by the anoxic release of potassium and excitatory amino acids from the infarct core, and they are propagated over the whole hemisphere at a speed of approximately 3 mm/min. The associated fluid shifts can be detected by diffusion-weighted magnetic resonance imaging (MRI) and correlate with an aggravation of the metabolic disturbance. In the peripheral, normally perfused brain regions of the infarcted hemisphere, the metabolic workload of SD is coupled to a parallel increase of blood flow, ensuring undisturbed oxygen supply. In the periinfarct penumbra, in contrast, the reduced hemodynamic capacity of the collateral system prevents adequate oxygenation and results in episodes of tissue hypoxia. Periinfarct SDs induce expression of immediate early genes in all brain regions except the ischemic core, i.e, in the penumbra and the surrounding normal brain tissue. In the penumbra, the hypoxic episodes evoked by SDs produce an additional stress response that is reflected by the expression of stress proteins and the suppression of global protein synthesis. In the most severely ischemic parts of the penumbra, periinfarct depolarizations may turn into terminal depolarization, resulting in a stepwise expansion of the infarct core. Postischemic application of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists suppresses periinfarct depolarizations, reverses the penumbral suppression of protein synthesis, and reduces infarct size. These observations demonstrate that periinfarct depolarizations aggravate focal ischemic injury and suggest that therapeutic suppression of these depolarizations minimizes infarct size.

Animals↗
PubMed1995

Calcium activity and post-ischemic suppression of protein synthesis.

Increase in intracellular calcium concentration is a prominent feature of ischemia and has been considered a major factor in the initiation of ischemic pathology, which involves inhibition of protein synthesis. A reduction of calcium ion activity during and immediately after in vitro ischemia did not prevent inhibition of protein synthesis in hippocampae slices. When slices were overloaded with calcium by NMDA receptor activation or by the calcium ionophore A23187, no significant inhibition of protein synthesis was observed. We conclude that calcium overload plays only a limited role in ischemic inhibition of protein synthesis.

Animals↗
PubMed1995

Simultaneous recording of EEG, DC potential and diffusion-weighted NMR imaging during potassium induced cortical spreading depression in rats.

Electrophysiological recording during in vivo NMR imaging for correlation of electrophysiological events with changes in NMR parameters has, until now, not been satisfactory. Here we present a method that uses specially prepared calomel electrodes for the continuous monitoring of both cortical steady potential and EEG during in vivo NMR imaging studies of experimental animal models. In order to demonstrate the reliability of this approach we elicited single episodes of cortical spreading depression in rats by intracortical potassium acetate injection, using an intracerebral micropipette. During the passage of DC potential shifts and associated reduction in EEG amplitude, hyperintense regions, reflecting the progression of cortical spreading depression over the cortex, were visible in diffusion-weighted images of the rat brains. No susceptibility artifacts due to the electrodes and micropipette were visible in the NMR data. Thus, we have demonstrated under controlled experimental conditions, that electrophysiological recording with calomel electrodes can be performed simultaneously with diffusion-weighted NMR imaging. The described method enables further NMR investigations of phenomena which are detectable by electrophysiology.

Animals↗
PubMed1995

Evolution of acute focal cerebral ischaemia in rats observed by localized 1H MRS, diffusion-weighted MRI, and electrophysiological monitoring.

Focal cerebral ischaemia was produced in 11 rats by permanent occlusion of the right middle cerebral artery (MCA) using a suture model modified to enable manipulation with the animals in situ in an NMR spectrometer. The development of the ischaemic insults and the resultant infarcts were observed for up to 6 h by localized 1H MRS and diffusion-weighted MRI while performing continuous monitoring of electroencephalogram and extracellular DC potential. The ischaemic areas were depicted as regions of hyperintensity in the diffusion-weighted images. Signals due to lactate became visible in the 1H spectra after MCA occlusion indicating the onset of anaerobic glycolysis. A depletion of N-acetylaspartate was seen in all animals post-occlusion. Transient or stepwise increases of lactate were observed to occur coincidentally with the events of spontaneous transient peri-infarct depolarization detected by the electrophysiological measurements. Expansion of the ischaemic area delineated in the diffusion-weighted images also accompanied peri-infarct depolarizations. These observations are consistent with transient peri-infarct depolarization playing a role in the growth of infarcts.

Acute Disease↗
PubMed1995

No-reflow after cardiac arrest.

OBJECTIVE: Successful resuscitation of the brain requires unimpaired blood recirculation. The study addresses the question of the severity and reversibility of no-reflow after cardiac arrest. DESIGN: Adult normothermic cats were submitted to 5, 15 and 30 min cardiac arrest by ventricular fibrillation. The extent of no-reflow was assessed in each cardiac arrest group after 5 min closed chest cardiac massage in combination with 0.2 mg/kg epinephrine or after successful resuscitation followed by 30 min recirculation. MEASUREMENTS AND RESULTS: Reperfusion of the brain was visualized by labelling the circulating blood with FITC-Albumin. Areas of no-reflow, defined as absence of microvascular filling, were identified by fluorescence microscopy at 8 standard coronal levels of forebrain, and expressed as percent of total sectional area. During cardiac massage, no-reflow affected 21 +/- 5%, 42 +/- 38% and 70 +/- 27% of forebrain after 5, 15 and 30 min cardiac arrest, respectively. After 30 min spontaneous recirculation following successful resuscitation of the heart, no-reflow significantly declined to 7 +/- 11% after 5 min cardiac arrest (p < 0.05) but persisted in 30 +/- 11% and 65 +/- 21% of forebrain after 15 and 30 min cardiac arrest, respectively (n.s.). CONCLUSION: Our observations demonstrate that resuscitation of the heart by closed chest massage causes severe (and after prolonged cardiac arrest irreversible) no-reflow of the brain. This suggests that no-reflow is an important cause of post-resuscitation brain pathology.

Analysis of Variance↗
PubMed1995

Effect of extracorporeal life support on cerebral blood flow, metabolism and electrophysiology in normothermic cats.

OBJECTIVE: Recently, extracorporeal life support (ECLS) by venoarterial bypass perfusion has been recommended for the treatment of refractory respiratory and/or cardiac failure but the safety of this application for the brain is not yet established. Therefore, the effects of normothermic ECLS on cerebral blood flow, metabolism and electrophysiology were studied in cats with total arrest of cardiopulmonary circulation. DESIGN: An extracorporeal circulation (ECC) system, consisting of a roller pump, a membrane oxygenator and a heat exchanger, was connected to the circulation of cat by cannulae inserted via the jugular vein and femoral vessels. After 2 h ECLS brains were frozen in situ and investigated for changes in regional metabolism. MEASUREMENTS AND RESULTS: During 2 h ECC hematocrit declined from 37 +/- 7% to 21 +/- 10% (means +/- SD, p < 0.05), cerebral blood flow decreased to 73 +/- 14% of control (p < 0.05) and cerebral oxygen delivery to 46 +/- 13% of control (p < 0.05) although arterial blood pressure and bypass flow rate did not change. Plasma lactate increased from 0.8 +/- 0.3 to 9.2 +/- 4.2 mumol/ml (p < 0.05), and brain tissue lactate from 2.3 +/- 0.9 to 10.6 +/- 2.7 mumol/g (p < 0.05). Hematocrit correlated positively with cerebral oxygen delivery (r = 0.86, p < 0.001). CONCLUSIONS: These data demonstrate that ECLS is associated with reduced cerebral oxygen delivery and may cause brain hypoxia despite normal blood pressure. This complication may contribute to the high incidence of neurological disturbances after prolonged ECLS.

Animals↗
PubMed1995

Diffusion-weighted MR imaging of experimental brain tumors in rats.

Diffusion-weighted magnetic resonance imaging was used for the description of experimental brain tumors in rat. To validate this approach, diffusion-weighted images (DWI) were compared with native T1- and T2-weighted images, and with T1-weighted images following contrast enhancement with the tumor-specific contrast agent manganese (III) tetraphenylporphine sulfonate (MnTPPS). Three tumor types were studied: F98 glioma, RN6 Schwannoma, and E376 neuroblastoma. On heavily diffusion-weighted images, all three tumor types as well as the peritumoral edema were clearly hypointense with respect to the intact brain tissue. T2-weighted images presented mainly peritumoral edema as hyperintense region. A clear demarcation of the tumor was possible only on T1-weighted images after contrast enhancement with MnTPPS. The difference in signal intensity between tumor and homotopic regions in the contralateral hemisphere was comparable in DWIs and in contrast-enhanced T1-weighted images. Spatial comparison of depicted lesion areas in all three imaging modalities indicated that hypointense region on DWI represents both tumor and edema but does not permit their spatial differentiation.

Animals↗
PubMed1995

Resuscitation from cardiac arrest in cats: influence of epinephrine dosage on brain recovery.

The quality of brain recovery after cardiac arrest depends crucially on the speed of cardiac resuscitation because the low cerebral perfusion pressure during the resuscitation procedure facilitates the development of no-reflow. To accelerate return of spontaneous circulation, high dose epinephrine has been recommended but the effect on the dynamics of early brain recovery is still unknown. We, therefore, studied the dynamics of brain resuscitation after cardiopulmonary resuscitation (CPR) with standard and high dose epinephrine using non-invasive NMR techniques. Fifteen min cardiac arrest was induced in normothermic cats by ventricular fibrillation. CPR was performed using an inflatable pneumatic vest for cyclic chest compression. With the beginning of CPR the standard dose group received 0.02 mg/kg epinephrine (n = 6) and the high dose group received 0.2 mg/kg (n = 8). Brain recovery was monitored by magnetic resonance imaging of the apparent diffusion coefficient (ADC) of water for 3 h. Although high dose epinephrine treatment led to a significantly higher blood pressure during early reperfusion, rapidly changing heterogeneities of early brain recovery were observed in both groups. High dose epinephrine thus does not improve the quality of post-cardiac arrest brain recovery during the first 3 h of reperfusion.

Animals↗
PubMed1995

Transient forebrain ischemia induces an immediate-early gene encoding the mitogen-activated protein kinase phosphatase 3CH134 in the adult rat brain.

In fibroblasts, serum stimulation has been shown to activate the immediate-early gene 3CH134 encoding a dual specificity protein phosphatase that regulates mitogen-activated protein kinase. We report here that 3CH134 messenger RNA levels increase during recirculation following 30 min forebrain ischemia in the rat brain. In normal rat brains, 3CH134 messenger RNA was found mainly in neurons of the cortex and thalamus. At recirculation periods up to 1 h after 30 min ischemia, 3CH134 messenger RNA increased in neurons and glial cells of all previously ischemic brain regions. After 3 and 6 h recirculation, a prominent increase of 3CH134 messenger RNA was observed in the pyramidal cell layer of all sectors of the hippocampus and the granule cells of the dentate gyrus, whereas in the other brain regions messenger RNA levels returned to control. Up to 6 h of recirculation the spatial induction pattern of 3CH134 was similar to the pattern observed for the immediate-early genes c-fos and c-jun. Within the hippocampus a similar pattern was also observed for the heat shock protein hsp70 messenger RNA. At 12 and 24 h after ischemia, increased levels of 3CH134 messenger RNA persisted in hippocampal neurons; at the same time a delayed increase of 3CH134 messenger RNA was observed in large neurons of the thalamus and in glial cells in damaged regions of the striatum. At later survival periods, 3CH134 messenger RNA returned to control levels. Our study shows that the mitogen-activated protein kinase phosphatase 3CH134 is induced in the brain after a period of global ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Relationship between diffusion-weighted MR images, cerebral blood flow, and energy state in experimental brain infarction.

The regional evolution of brain infarction was studied in Wistar rats submitted to remotely controlled thread occlusion of the middle cerebral artery. Occlusion was performed in the magnet of an NMR tomography system to allow continuous recording of diffusion-weighted images. After 30 min (n = 6) or 2 h (n = 9), cerebral blood flow was measured by [14C] iodoantipyrine autoradiography while the regional distribution of ATP, glucose, lactate, and pH was imaged using pictorial bioluminescence and fluoroscopic methods. In diffusion-weighted images, the hemispheric lesion area (HLA) at the level of caudate-putamen amounted to 54.2 +/- 10.9% after 30 min and to 67.0 +/- 5.9% after 2 h vascular occlusion. These areas corresponded to the regions exhibiting tissue acidosis (60.8 +/- 9.3% and 70.4 +/- 4.5%), but were clearly larger than those in which ATP was depleted (22.3 +/- 20.8% and 49.6 +/- 12.9% after 30 min and 2 h, respectively). The threshold of blood flow for the increase of signal intensity in diffusion-weighted images increased between 30 min and 2 h occlusion from 34 to 41 ml/100 g per minute, the threshold of acidosis from 40 to 47 ml/100 g per minute, and the threshold for ATP depletion from 13 to 19 ml/100 g per minute. Our study demonstrates that diffusion-weighted imaging detects both the core and the penumbra of the evolving infarction but is not able to differentiate between the two parts. It further shows that the ischemic lesion grows during the initial 2 h of vascular occlusion, and that the size of the infarct core increases more rapidly than that of the penumbra.

Adenosine Triphosphate↗